The present invention is directed to a container system, and more particularly to a container system for liquid reagents used in performing assays on a medical diagnostic apparatus, wherein the liquid reagents can be lyophilized.
The analysis of plasma or other fluid from a patient can provide a physician with valuable information about the patient's medical condition. Typically, a blood sample is withdrawn from a patient into a vacuum sample tube, which is sent to a laboratory in order to perform specific diagnostic assays. The assays are performed by treating the sample with various reagents, buffer solutions, and control and calibration liquids. Automated diagnostic machines are commonly used to perform the assays in a highly reliable and automatic manner.
Reagents which contain biologically active materials such as proteins and enzymes are used in many assays. Often, these types of reagents must be very pure and have a specified potency. These requirements are difficult to fulfill since biologically active material can be easily damaged.
Certain reagents in liquid form deteriorate at an undesirably rapid rate and are lyophilized to improve long term stability. Alternatively, acceptable quality can be maintained if the reagents are frozen, but this poses obvious problems in distribution and storage of the reagents. Furthermore, frozen reagents would have to be thawed under controlled conditions before use in assays, and the time required of skilled technicians would increase costs. For these reasons it has become common in the art to prepare reagents in dried form by a procedure called "lyophilization." In this "freeze drying" procedure, water is extracted from a reagent that is cooled and exposed to vacuum. The extraction of the moisture leaves a dry powder of biologically active material which can have a room-temperature shelf life of years, depending on the reagent.
Conventionally, lyophilization of a reagent is done in a glass vial with a flat base that supports the vial in an upright position during the procedure. Glass has been the material of choice since it is a good heat conductor, a factor which facilitates the lyophilization process. It is also impervious to water. However, glass vials are fragile and can be relatively expensive to manufacture to stringent specifications. Glass can also denature certain proteins due to its surface charge characteristics.
It has been considered impractical to use plastic instead of glass as the vial. Until recently, plastics were not as impervious to moisture as needed for the lyophilization, nor were they able to sustain their molded shape when subjected to the conditions of heat and vacuum that occur during lyophilization.
Prior to use, the lyophilized reagent is reconstituted by adding a liquid, such as a buffer or water, to the vial. Because of the flat-bottomed shape, appreciable quantities of expensive reagents remain in the bottom of the vial when the vial is used on an automated machine.
A blow-molded plastic vial for medical substances has recently been introduced by Abbott Laboratories. It is believed that the plastic employed is incompatible with lyophilization of reagents in the vial. The vial is slightly over five centimeters tall and has an outer diameter of slightly over two centimeters. The vial has a top portion configured to accept a screw-on cap, a cylindrical intermediate portion, and an inwardly tapering bottom portion. The bottom portion includes a conical region which has a very obtuse apex angle (considerably more than 90.degree.) and which rises from a cone tip to an annular bead. The annular bead of the bottom portion is followed upwardly by an annular groove disposed just below the cylindrical intermediate portion of the vial. A plastic auxiliary member, which includes a disc-shaped portion connected to one end of a cylindrical portion, is configured to snap onto the bottom portion of the vial to provide the vial with a flat bottom surface. Once attached, the auxiliary member cannot be pried off without difficulty. The cone tip of the vial is spaced apart from the disc-shaped portion of the auxiliary member by an air gap when the auxiliary member is snapped onto the vial. Such an air gap has an insulating quality that retards heat transfer through the bottom portion of the vial. The disc-shaped portion of the auxiliary member has a small breather hole that is disposed at an eccentric position, near the cylindrical portion of the auxiliary member. This breather hole is the sole aperture in the disc-shaped portion.
Glass vials are generally sealed with stoppers that are secured by crimped metal covers. One type of cover can be removed by pulling a metal tab off of the top. As sharp edges are then exposed, it is possible that the personnel dealing with these types of covers can be cut and exposed to toxic chemicals in the laboratory.